TsDPENs

On the other hand, one of the first chiral sulfur-containing ligands employed in the asymmetric transfer hydrogenation of ketones was introduced by Noyori el al Thus, the use of A-tosyl-l,2-diphenylethylenediamine (TsDPEN) in combination with ruthenium for the reduction of various aromatic ketones in the presence of i-PrOH as the hydrogen donor, allowed the corresponding alcohols to be obtained in both excellent yields and enantioselectivities, as... 

As another successful application of Noyori s TsDPEN ligand, Yan et al. reported the synthesis of antidepressant duloxetine, in 2008. Thus, the key step of this synthesis was the asymmetric transfer hydrogenation of 3-(dime-thylamino)-l-(thiophen-2-yl)propan-l-one performed in the presence of (5,5)-TsDPEN Ru(II) complex and a HCO2H TEA mixture as the hydrogen donor. The reaction afforded the corresponding chiral alcohol in both high yield and enantioselectivity, which was further converted in two steps into expected (5)-duloxetine, as shown in Scheme 9.17. 

In order to improve the performance of Noyori s catalytic system, Ru(II)-TsDPEN, which is very efficient but suffers from a long reaction time and a low activity in some cases, Mohar et al. have modified the diamine ligand by... 

Scheme 9.15 Ru-catalysed reductions of ketones with TsDPEN ligand.

Scheme 9.23 Ru-catalysed DKR-reductions of cyclic a-haloketones with TsDPEN ligand.

The first example of an asymmetric reduction of C=N bonds proceeding via DKR was reported in 2005 by Lassaletta et al. In this process, the transfer hydrogenation of 2-substituted bicyclic and monocyclic ketimines could be accomplished via DKR by using a HCO2H/TEA mixture as the hydrogen source and a chiral ruthenium complex including TsDPEN ligand,... 

In many cases the solvent was observed to have a large effect on the optical purity of the product. Examples of this, with a ketone and the rhodium cp TsDPEN catalyst, are shown in Table 35.3. Further optimization of this reaction improved the enantiomeric excess to 98%. A second example involved the reduction of 4-fluoroacetophenone in this case the enantioselectivity was largely unaffected, but the rate of reduction changed markedly with solvent. Development of this process improved the optical purity to 98.5% ee. 

---